Richard A Rudick1, Sha Mi, Alfred W Sandrock. 1. Mellen Center for Multiple Sclerosis Treatment and Research, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA. rudickr@ccf.org
Abstract
BACKGROUND: Multiple sclerosis (MS) is an inflammatory disease of the CNS that causes progressive neurological disability in most patients. Certain alleles of immunity-associated genes increase risk of MS, confirming a role for autoimmune mechanisms in pathogenesis. Activated mononuclear cells infiltrate the CNS and trigger an inflammatory cascade, resulting in demyelination and axonal injury. Non-inflammatory mechanisms also appear to be involved in axonal degeneration but are not fully elucidated. Current therapies are anti-inflammatory, and no available therapy is known to promote myelin repair or maintenance. Leucine-rich repeats and Ig domain-containing, neurite outgrowth inhibitor (Nogo) receptor-interacting protein-1 (LINGO-1) is a potent negative regulator of axonal myelination. OBJECTIVE/ METHODS: This article provides an overview of the available data on the effects of LINGO-1 antagonists on oligodendrocyte differentiation and remyelination. RESULTS/ CONCLUSION: LINGO-1 is a potential target for neuroprotective therapy in that antagonists may promote remyelination in diseases such as MS.
BACKGROUND:Multiple sclerosis (MS) is an inflammatory disease of the CNS that causes progressive neurological disability in most patients. Certain alleles of immunity-associated genes increase risk of MS, confirming a role for autoimmune mechanisms in pathogenesis. Activated mononuclear cells infiltrate the CNS and trigger an inflammatory cascade, resulting in demyelination and axonal injury. Non-inflammatory mechanisms also appear to be involved in axonal degeneration but are not fully elucidated. Current therapies are anti-inflammatory, and no available therapy is known to promote myelin repair or maintenance. Leucine-rich repeats and Ig domain-containing, neurite outgrowth inhibitor (Nogo) receptor-interacting protein-1 (LINGO-1) is a potent negative regulator of axonal myelination. OBJECTIVE/ METHODS: This article provides an overview of the available data on the effects of LINGO-1 antagonists on oligodendrocyte differentiation and remyelination. RESULTS/ CONCLUSION:LINGO-1 is a potential target for neuroprotective therapy in that antagonists may promote remyelination in diseases such as MS.
Authors: Kelly A Chamberlain; Sonia E Nanescu; Konstantina Psachoulia; Jeffrey K Huang Journal: Neuropharmacology Date: 2015-10-22 Impact factor: 5.250
Authors: L Cobret; M L De Tauzia; J Ferent; E Traiffort; I Hénaoui; F Godin; E Kellenberger; D Rognan; J Pantel; H Bénédetti; S Morisset-Lopez Journal: Br J Pharmacol Date: 2014-12-15 Impact factor: 8.739